We examined the responsiveness of two factor-dependent macrophage cell lines, BDM-1 and its subclone, BDM-1W3, to bacterial lipopolysaccharide (LPS), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) for their growth. LPS inhibited the M-CSF-dependent proliferation of BDM-1 cells but it had no effect on the proliferation of BDM-1W3 cells. LPS promoted DNA synthesis and supported the cell viability in the absence of CSFs in BDM-1 and BDM-1W3 cells, suggesting that the intracellular signals are transduced from the interaction of LPS with LPS-binding sites in BDM-1W3 cells as well as in BDM-1 cells. IFN-γ inhibited the proliferation of BDM-1 and BDM-1W3 cells. However, BDM-1 cells were more susceptible to the inhibitory effect of IFN-γ than BDM-1W3 cells. In contrast to LPS and IFN-γ, TNF-α did not inhibit the proliferation of BDM-1 and BDM-1W3 cells. These cell lines should be useful for studying the regulatory mechanisms in CSF-dependent macrophage proliferation.